Research on Online Monitoring Technology and Filtration Process of Inclusions in Aluminum Melt.

Online monitoring and real-time feedback on inclusions in molten metal are essential for metal quality control. However, existing methods for detecting aluminum melt inclusions face challenges, including interference, prolonged processing times, and latency. This paper presents the design and development of an online monitoring system for molten metal inclusions. Initially, the system facilitates real-time adjustment of signal acquisition parameters through a multiplexer. Subsequently, it employs a detection algorithm capable of swiftly extracting pulse peaks, with this task integrated into our proprietary host computer software to ensure timely detection and data visualization. Ultimately, we developed a monitoring device integrated with this online monitoring system, enabling the online monitoring of the aluminum alloy filtration process. Our findings indicate that the system can accurately measure the size and concentration of inclusions during the filtration process in real time, offering enhanced detection speed and stability compared to the industrial LiMCA CM (liquid metal cleanliness analyzer continuous monitoring) standard. Furthermore, our evaluation of the filtration process demonstrates that the effectiveness of filtration significantly improves with the increase in inclusion sizes, and the synergistic effect of combining CFF (ceramic foam filter) and MCF (metallics cartridge filter) filtration methods exceeds the performance of the CFF method alone. This system thus provides valuable technical support for optimizing filtration processes and controlling inclusion quality.

An Online Monitoring System for In Situ and Real-Time Analyzing of Inclusions within the Molten Metal.

Traditional methods for assessing the cleanliness of liquid metal are characterized by prolonged detection times, delays, and susceptibility to variations in sampling conditions. To address these limitations, an online cleanliness-analyzing system grounded in the method of the electrical sensing zone has been developed. This system facilitates real-time, in situ, and quantitative analysis of inclusion size and amount in liquid metal. Comprising pneumatic, embedded, and host computer modules, the system supports the continuous, online evaluation of metal cleanliness across various metallurgical processes in high-temperature environments. Tests conducted with gallium liquid at 90 °C and aluminum melt at 800 °C have validated the system's ability to precisely and quantitatively detect inclusions in molten metal in real time. The detection procedure is stable and reliable, offering immediate data feedback that effectively captures fluctuations in inclusion amount, thereby meeting the metallurgical industry's demand for real-time analyzing and control of inclusion cleanliness in liquid metal. Additionally, the system was used to analyze inclusion size distribution during the hot-dip galvanizing process. At a zinc melt temperature of 500 °C, it achieved a detection limit of 21 µm, simultaneously providing real-time data on the size and amount distribution of inclusions. This represents a novel strategy for the online monitoring and quality control of zinc slag throughout the hot-dip galvanizing process.

Effect of loops on the mean-square displacement of Rouse-model chromatin.

Chromatin polymer dynamics are commonly described using the classical Rouse model. The subsequent discovery, however, of intermediate-scale chromatin organization known as topologically associating domains (TADs) in experimental Hi-C contact maps for chromosomes across the tree of life, together with the success of loop extrusion factor (LEF) model in explaining TAD formation, motivates efforts to understand the effect of loops and loop extrusion on chromatin dynamics. This paper seeks to fulfill this need by combining LEF-model simulations with extended Rouse-model polymer simulations to investigate the dynamics of chromatin with loops and dynamic loop extrusion. We show that loops significantly suppress the averaged mean-square displacement (MSD) of a gene locus, consistent with recent experiments that track fluorescently labeled chromatin loci. We also find that loops reduce the MSD's stretching exponent from the classical Rouse-model value of 1/2 to a loop-density-dependent value in the 0.45-0.40 range. Remarkably, stretching exponent values in this range have also been observed in recent experiments [Weber et al., Phys. Rev. Lett. 104, 238102 (2010)0031-900710.1103/PhysRevLett.104.238102; Bailey et al., Mol. Biol. Cell 34, ar78 (2023)1059-152410.1091/mbc.E23-04-0119]. We also show that the dynamics of loop extrusion itself negligibly affects chromatin mobility. By studying static "rosette" loop configurations, we also demonstrate that chromatin MSDs and stretching exponents depend on the location of the locus in question relative to the position of the loops and on the local friction environment.

Inverse design of a pyrochlore lattice of DNA origami through model-driven experiments.

Sophisticated statistical mechanics approaches and human intuition have demonstrated the possibility of self-assembling complex lattices or finite-size constructs. However, attempts so far have mostly only been successful in silico and often fail in experiment because of unpredicted traps associated with kinetic slowing down (gelation, glass transition) and competing ordered structures. Theoretical predictions also face the difficulty of encoding the desired interparticle interaction potential with the experimentally available nano- and micrometer-sized particles. To overcome these issues, we combine SAT assembly (a patchy-particle interaction design algorithm based on constrained optimization) with coarse-grained simulations of DNA nanotechnology to experimentally realize trap-free self-assembly pathways. We use this approach to assemble a pyrochlore three-dimensional lattice, coveted for its promise in the construction of optical metamaterials, and characterize it with small-angle x-ray scattering and scanning electron microscopy visualization.

Extracellular release of mitochondria induced by pre-hematopoietic stem cell transplant conditioning exacerbates GVHD.

Despite therapeutic advancements, GVHD is a major complication of HSCT. In current models of GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation of microbes expressing Pathogen Associated Molecular Patterns (PAMPs), result in activation of host antigen-presenting cells (APC) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that in many pathologic states, tissue injury results in the release of mitochondria from the cytoplasm to the extracellular space. We hypothesized that extracellular mitochondria, which are related to archaebacteria, could also trigger GVHD by stimulation of host APC. We found that clinically relevant doses of radiation or busulfan induced extracellular release of mitochondria by various cell types, including cultured intestinal epithelial cells. Conditioning-mediated mitochondrial release was associated with mitochondrial damage and impaired quality control but did not affect the viability of the cells. Extracellular mitochondria directly stimulated host APCs to express higher levels of MHC-II, co-stimulatory CD86, and pro-inflammatory cytokines, resulting in increased donor T cell activation, and proliferation in mixed lymphocyte reactions. Analyses of plasma from both experimental mice and a cohort of children undergoing HSCT demonstrated that conditioning induced extracellular mitochondrial release in vivo. In mice undergoing MHC mismatched HSCT, administration of purified syngeneic extracellular mitochondria increased host APC activation and exacerbated GVHD. Our data suggests that pre-HSCT conditioning results in extracellular release of damaged mitochondria which increase alloreactivity and exacerbate GVHD. Therefore, decreasing the extracellular release of damaged mitochondria following conditioning could serve as a novel strategy for GVHD prevention.

Low neutralization of SARS-CoV-2 Omicron BA.5.2.48 and XBB.1 sub-variants in response to breakthrough infection by booster.

To assess the levels of and neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its mutants in serum samples from patients with breakthrough infection. Sixty-four patients with breakthrough infections were recruited for this cross-sectional study. All samples were used to neutralizing antibodies (nAbs) against SARS-CoV-2 and its mutants using a focused reduction neutralization assay. A total of 512 serum samples were obtained from unvaccinated patients who received one dose of vaccine (n = 12), received two doses of vaccine (n = 15), and received three doses of vaccine (n = 37). The geometric mean titer (GMT) of neutralizing antibodies against the Omicron subvariant was significantly lower (GMT 66.8 and 56.1) compared to the original strain, regardless of whether two or three doses of vaccine were administered. This result highlights that sera from breakthrough infections induce broad neutralization, but Omicron XBB.1.16 exhibits high immune evasion potential.

Recent advances in nanomaterial-stabilized pickering foam: Mechanism, classification, properties, and applications.

Pickering foam is a type of foam stabilized by solid particles known as Pickering stabilizers. These solid stabilizers adsorb at the liquid-gas interface, providing superior stability to the foam. Because of its high stability, controllability, versatility, and minimal environmental impact, nanomaterial-stabilized Pickering foam has opened up new possibilities and development prospects for foam applications. This review provides an overview of the current state of development of Pickering foam stabilized by a wide range of nanomaterials, including cellulose nanomaterials, chitin nanomaterials, silica nanoparticles, protein nanoparticles, clay mineral, carbon nanotubes, calcium carbonate nanoparticles, MXene, and graphene oxide nanosheets. Particularly, the preparation and surface modification methods of various nanoparticles, the fundamental properties of nanomaterial-stabilized Pickering foam, and the synergistic effects between nanoparticles and surfactants, functional polymers, and other additives are systematically introduced. In addition, the latest progress in the application of nanomaterial-stabilized Pickering foam in the oil industry, food industry, porous functional material, and foam flotation field is highlighted. Finally, the future prospects of nanomaterial-stabilized Pickering foam in different fields, along with directions for further research and development directions, are outlined.

Dabrafenib Alleviates Hepatotoxicity Caused by Lenvatinib via Inhibiting the Death Receptor Signaling Pathway.

Lenvatinib is a multi-target inhibitor that exerts anti-tumor effects by inhibiting angiogenesis and is now commonly used as a first-line treatment for hepatocellular carcinoma. However, with the widespread use of lenvatinib, the problem of serious and fatal hepatotoxicity has become increasingly prominent. Currently, the mechanism behind this toxicity is not yet understood, and as a result, there is a lack of safe and effective intervention strategies with minimal side effects. Here, we established the model of lenvatinib-induced liver injury in vivo and in vitro and found that lenvatinib caused hepatotoxicity by inducing apoptosis. Further mechanistic studies in cellular models revealed that lenvatinib upregulated death receptor signaling pathway, which activated the downstream effector Caspase-8, and ultimately led to apoptosis. Meanwhile, lenvatinib-induced apoptosis was associated with ROS generation and DNA damage. In addition, after screening marketed drugs and natural products in combination with cellular modeling, we identified a potential co-administered drug, dabrafenib, which could alleviate lenvatinib-induced hepatotoxicity. Further mechanistic studies revealed that dabrafenib attenuated lenvatinib-induced hepatotoxicity by inhibiting the activation of the death receptor signaling pathway. Subsequently, cancer cell proliferation assays confirmed that dabrafenib did not antagonize the antitumor effects of lenvatinib. In conclusion, our results validate that apoptosis caused by the death receptor signaling pathway is the key cause of lenvatinib-induced hepatotoxicity, and dabrafenib alleviates lenvatinib-induced hepatotoxicity by inhibiting this pathway.

PTEN and P-4E-BP1 might be associated with postoperative recurrence of rectal cancer patients undergoing concurrent radiochemotherapy.

BACKGROUND: Local recurrence after surgery and radiochemotherapy seriously affects the prognosis of locally advanced rectal cancer (LARC) patients. Studies on molecular markers related to the radiochemotherapy sensitivity of cancers have been widely carried out, which might provide valued information for clinicians to carry out individual treatment. AIM: To find potential biomarkers of tumors for predicting postoperative recurrence. METHODS: In this study, LARC patients undergoing surgery and concurrent radiochemotherapy were enrolled. We focused on clinicopathological factors and PTEN, SIRT1, p-4E-BP1, and pS6 protein expression assessed by immunohistochemistry in 73 rectal cancer patients with local recurrence and 76 patients without local recurrence. RESULTS: The expression of PTEN was higher, while the expression of p-4E-BP1 was lower in patients without local recurrence than in patients with local recurrence. Moreover, TNM stage, lymphatic vessel invasion (LVI), PTEN and p-4E-BP1 might be independent risk factors for local recurrence after LARC surgery combined with concurrent radiochemotherapy. CONCLUSIONS: This study suggests that PTEN and p-4E-BP1 might be potential biomarkers for prognostic prediction and therapeutic targets for LARC.

Three-dimensional laser micromachining system with integrated sub-100†nm resolution in-situ measurement.

In this study, a three-dimensional (3D) laser micromachining system with an integrated sub-100 nm resolution in-situ measurement system was proposed. The system used the same femtosecond laser source for in-situ measurement and machining, avoiding errors between the measurement and the machining positions. It could measure the profile of surfaces with an inclination angle of less than 10°, and the measurement resolution was greater than 100 nm. Consequently, the precise and stable movement of the laser focus could be controlled, enabling highly stable 3D micromachining. The results showed that needed patterns could be machined on continuous surfaces using the proposed system. The proposed machining system is of great significance for broadening the application scenarios of laser machining.

In Situ Electrochemical Atomic Force Microscopy: From Interfaces to Interphases.

The electrochemical interface formed between an electrode and an electrolyte significantly affects the rate and mechanism of the electrode reaction through its structure and properties, which vary across the interface. The scope of the interface has been expanded, along with the development of energy electrochemistry, where a solid-electrolyte interphase may form on the electrode and the active materials change properties near the surface region. Developing a comprehensive understanding of electrochemical interfaces and interphases necessitates three-dimensional spatial resolution characterization. Atomic force microscopy (AFM) offers advantages of imaging and long-range force measurements. Here we assess the capabilities of AFM by comparing the force curves of different regimes and various imaging modes for in situ characterizing of electrochemical interfaces and interphases. Selected examples of progress on work related to the structures and processes of electrode surfaces, electrical double layers, and lithium battery systems are subsequently illustrated. Finally, this review provides perspectives on the future development of electrochemical AFM.

Development of a group II intron-based genetic manipulation tool for Streptomyces.

The availability of an alternative and efficient genetic editing technology is critical for fundamental research and strain improvement engineering of Streptomyces species, which are prolific producers of complex secondary metabolites with significant pharmaceutical activities. The mobile group II introns are retrotransposons that employ activities of catalytic intron RNAs and intron-encoded reverse transcriptase to precisely insert into DNA target sites through a mechanism known as retrohoming. We here developed a group II intron-based gene editing tool to achieve precise chromosomal gene insertion in Streptomyces. Moreover, by repressing the potential competition of RecA-dependent homologous recombination, we enhanced site-specific insertion efficiency of this tool to 2.38%. Subsequently, we demonstrated the application of this tool by screening and characterizing the secondary metabolite biosynthetic gene cluster (BGC) responsible for synthesizing the red pigment in Streptomyces roseosporus. Accompanied with identifying and inactivating this BGC, we observed that the impair of this cluster promoted cell growth and daptomycin production. Additionally, we applied this tool to activate silent jadomycin BGC in Streptomyces venezuelae. Overall, this work demonstrates the potential of this method as an alternative tool for genetic engineering and cryptic natural product mining in Streptomyces species.

Childhood urbanicity is associated with emotional episodic memory-related striatal function and common variation in NTRK2.

BACKGROUND: Childhoods in urban or rural environments may differentially affect the risk of neuropsychiatric disorders, possibly through memory processing and neural response to emotional stimuli. Genetic factors may not only influence individuals' choices of residence but also modulate how the living environment affects responses to episodic memory. METHODS: We investigated the effects of childhood urbanicity on episodic memory in 410 adults (discovery sample) and 72 adults (replication sample) with comparable socioeconomic statuses in Beijing, China, distinguishing between those with rural backgrounds (resided in rural areas before age 12 and relocated to urban areas at or after age 12) and urban backgrounds (resided in cities before age 12). We examined the effect of childhood urbanicity on brain function across encoding and retrieval sessions using an fMRI episodic memory paradigm involving the processing of neutral or aversive pictures. Moreover, genetic association analyses were conducted to understand the potential genetic underpinnings that might contribute to memory processing and neural mechanisms influenced by early-life urban or rural environments. RESULTS: Episodic memory retrieval accuracy for more difficult neutral stimuli was similar between those with urban and rural childhoods, whereas aversive stimuli elicited higher retrieval accuracy in the urban group (P = 0.023). For aversive stimuli, subjects with urban childhood had relatively decreased engagement of the striatum at encoding and decreased engagement of the hippocampus at retrieval. This more efficient striatal encoding of aversive stimuli in those with urban childhoods was associated with common variation in neurotrophic tyrosine kinase receptor type 2 (NTRK2) (right striatum: P = 1.58×10-6). These findings were confirmed in the replication sample. CONCLUSIONS: We suggest that this differential striatal processing of aversive stimuli observed in individuals with urban or rural childhoods may represent mechanisms by which childhood urbanicity may affect brain circuits, heightening behavioral responses to negative stressors associated with urban environments. NTRK2-associated neural processes in the striatum may play a role in these processes.

Synergistic Strain Suppressing and Interface Engineering in Na4MnV(PO4)3/C for Wide-Temperature and Long-Calendar-Life Sodium-Ion Storage.

A Na4MnV(PO4)3 (NMVP) cathode is regarded as a promising cathode candidate for sodium-ion batteries (SIBs). However, issues such as low electronic conductivity and partial cation dissolution contribute to high polarization and structure distortion. Herein, we engineered the local electron density and reaction kinetic properties of NMVP cathodes with varying oxygen vacancies by introducing varying amounts of Zr doping and carbon coating. The optimized sample exhibited a high-rate capacity of 71.8 mAh g-1 at 30 C (83.1% capacity retention after 1000 cycles) and excellent performance over a wide temperature range (84.1 mAh g-1 at 60 °C and 61.4 mAh g-1 at -30 °C). In situ X-ray diffraction technology confirmed a redox solid solution and a two-phase reaction mechanism, revealing minor changes in cell volume and slight strain variations after Zr doping, effectively suppressing the structural distortion. Theoretical calculations illustrated that Zr doping largely shrinks the band gap of NMVP, enriches local electron density, and slightly alters the local element distribution and bond lengths. Moreover, full-cells have shown high energy density (259.9 Wh kg-1) and outstanding cycling stability (200 cycles). The work provides fresh insights into the synergistic effect of strain suppressing and interface engineering in promoting the development of wide temperature range and long-calendar-life SIBs.

Effect of probiotic administration during pregnancy on the functional diversity of the gut microbiota in healthy pregnant women.

Our study aims to investigate the impact of probiotic consumption during pregnancy on gut microbiota functional diversity in healthy pregnant women. Thirty-two pregnant women were randomly assigned to two groups. The probiotic group (PG) consisted of pregnant women who consumed triple viable Bifidobacterium longum, Lactobacillus delbrueckii bulgaricus, and Streptococcus thermophilus tablets from the 32nd week of pregnancy until delivery. The functional profiles of the gut microbiota were predicted through high-throughput 16S rRNA sequencing results using PICRUSt software and referencing the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. In the gut microbiota of the PG, the genera Blautia and Ruminococcus, as well as the species Subdoligranulum, showed significantly higher relative abundances compared to the control group (CG) (P < 0.05). At Level 1 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Organismal Systems in the PG (P < 0.05). In Level 2 of the KEGG signaling pathways, there was a significant reduction in the functional genes of the gut microbiota involved in Infectious Disease in the PG (P < 0.05). In Level 3 of the KEGG signaling pathways, the PG exhibited a significant increase in the functional genes of the gut microbiota involved in ABC transporters, Oxidative phosphorylation, Folate biosynthesis, and Biotin metabolism (P < 0.05). The CG showed a significant increase in the functional genes related to Cysteine and methionine metabolism, Vitamin B6 metabolism, Tuberculosis, and Vibrio cholerae pathogenic cycle (P < 0.05). In conclusion, our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism in healthy pregnant women. IMPORTANCE: Probiotics are considered beneficial to human health. There is limited understanding of how probiotic consumption during pregnancy affects the functional diversity of the gut microbiota. The aim of our study is to investigate the impact of probiotic consumption during pregnancy on the functional diversity of the gut microbiota. Our findings suggest that probiotic supplementation during pregnancy has a significant impact on functional metabolism. This could potentially open up new avenues for preventing various pregnancy-related complications. This also provides new insights into the effects of probiotic consumption during pregnancy on the gut microbiota and offers a convenient method for exploring the potential mechanisms underlying the impact of probiotics on the gut microbiota of pregnant women.

Tumor microenvironment activated mussel-inspired hollow mesoporous nanotheranostic for enhanced synergistic photodynamic/chemodynamic therapy.

Anti-tumor therapies reliant on reactive oxygen species (ROS) as primary therapeutic agents face challenges due to a limited oxygen substrate. Photodynamic therapy (PDT) is particularly hindered by inherent hypoxia, while chemodynamic therapy (CDT) encounters obstacles from insufficient endogenous hydrogen peroxide (H2O2) levels. In this study, we engineered biodegradable tumor microenvironment (TME)-activated hollow mesoporous MnO2-based nanotheranostic agents, designated as HAMnO2A. This construct entails loading artemisinin (ART) into the cavity and surface modification with a mussel-inspired polymer ligand, namely hyaluronic acid-linked poly(ethylene glycol)-diethylenetriamine-conjugated (3,4-dihydroxyphenyl) acetic acid, and the photosensitizer Chlorin e6 (mPEG-HA-Dien-(Dhpa/Ce6)), facilitating dual-modal imaging-guided PDT/CDT synergistic therapy. In vitro experimentation revealed that HAMnO2A exhibited ideal physiological stability and enhanced cellular uptake capability via CD44-mediated endocytosis. Additionally, it was demonstrated that accelerated endo-lysosomal escape through the pH-dependent protonation of Dien. Within the acidic and highly glutathione (GSH)-rich TME, the active component of HAMnO2A, MnO2, underwent decomposition, liberating oxygen and releasing both Mn2+ and ART. This process alleviates hypoxia within the tumor region and initiates a Fenton-like reaction through the combination of ART and Mn2+, thereby enhancing the effectiveness of PDT and CDT by generating increased singlet oxygen (1O2) and hydroxyl radicals (•OH). Moreover, the presence of Mn2+ ions enabled the activation of T1-weighted magnetic resonance imaging. In vivo findings further validated that HAMnO2A displayed meaningful tumor-targeting capabilities, prolonged circulation time in the bloodstream, and outstanding efficacy in restraining tumor growth while inducing minimal damage to normal tissues. Hence, this nanoplatform serves as an efficient all-in-one solution by facilitating the integration of multiple functions, ultimately enhancing the effectiveness of tumor theranostics.

Mechanism of KDM5A-mediated H3K4me3 modification in the osteogenic differentiation of mesenchymal stem cells in steroid-induced osteonecrosis of the femoral head.

OBJECTIVES: Steroid-induced osteonecrosis of the femoral head (SONFH) is characterized by impaired osteogenesis in bone marrow mesenchymal stem cells (BMSCs). This study investigates the role of lysine-specific demethylase 5A (KDM5A) in SONFH to identify potential therapeutic targets. METHODS: Human BMSCs were isolated and characterized for cell surface markers and differentiation capacity. A SONFH cell model was established using dexamethasone treatment. BMSCs were transfected with KDM5A overexpression vectors or si-KDM5A, and the expression of KDM5A, miR-107, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) was assessed. Alizarin red staining was used to observe mineralization nodules, while alkaline phosphatase activity and cell viability were measured. The enrichment of KDM5A and histone 3 lysine 4 trimethylation (H3K4me3) on the promoters of RUNX2, OCN, and OPN was analyzed. The binding between miR-107 and KDM5A 3'UTR was validated, and the combined effect of miR-107 overexpression and KDM5A overexpression on BMSC osteogenic differentiation was evaluated. RESULTS: KDM5A was upregulated in BMSCs from SONFH. Inhibition of KDM5A promoted osteogenic differentiation of BMSCs, associated with increased RUNX2, OCN, and OPN promoters. KDM5A bound to the promoters of RUNX2, OCN, and OPN, leading to reduced H3K4me3 levels and downregulation of their expression. Overexpression of miR-107 inhibited KDM5A and enhanced BMSC osteogenic differentiation. CONCLUSION: KDM5A negatively regulates BMSC osteogenic differentiation by modulating H3K4me3 levels on the promoters of key osteogenic genes. miR-107 overexpression counteracts the inhibitory effect of KDM5A on osteogenic differentiation. These findings highlight the potential of targeting the KDM5A/miR-107 axis for SONFH therapy.

Association between sarcopenic obesity and mortality in patients on peritoneal dialysis: a prospective cohort study.

Background: Whether sarcopenic obesity had unfavorable effect on survival of peritoneal dialysis (PD) patients is unknown. We aimed to investigate the association between sarcopenic obesity and survival in PD patients. Methods: This was a prospective observational study. Eligible PD patients from November 2016 to December 2017 were enrolled and followed until August 31, 2023. Sarcopenia was defined following the recommendations of the Asian Working Group for Sarcopenia (AWGS) as low appendicular skeletal muscle mass index (ASMI) and handgrip strength (HGS). Obesity was defined using the percentage of body fat (PBF). Survival analysis was conducted using the Kaplan-Meier and log-rank test. The Cox regression and the cumulative incidence competing risk (CICR) analyzes were used to investigate the association between sarcopenic obesity and all-cause mortality. Results: A total of 223 patients were enrolled with 133 (59.6%) males, a median age of 57.5 (44.6, 65.7) years, a median dialysis vintage of 20.3 (6.4, 57.7) months and 48 (21.5%) who had comorbid diabetes mellitus. Among them, 46 (20.6%) patients were sarcopenic, and 25 (11.2%) patients were diagnosed with sarcopenic obesity. After followed up for 51.6 (25.6, 73.9) months, the Kaplan-Meier curve showed the sarcopenic obesity (log-rank = 13.527, p < 0.001) group had significant lower survival rate compared to the nonsarcopenic non-obesity group. For multivariate analysis, the CICR method showed patients with sarcopenic obesity had significantly higher mortality rate (HR: 2.190, 95% CI: 1.011-4.743, p = 0.047) compared to those with nonsarcopenic non-obesity. Conclusion: Sarcopenia is not uncommon in PD patients, with a considerable proportion having sarcopenic obesity. There is a significant association between sarcopenic obesity and an increased risk of mortality in PD patients.

Discovery of a selective TRF2 inhibitor FKB04 induced telomere shortening and senescence in liver cancer cells.

Telomere repeat binding factor 2 (TRF2), a critical element of the shelterin complex, plays a vital role in the maintenance of genome integrity. TRF2 overexpression is found in a wide range of malignant cancers, whereas its down-regulation could cause cell death. Despite its potential role, the selectively small-molecule inhibitors of TRF2 and its therapeutic effects on liver cancer remain largely unknown. Our clinical data combined with bioinformatic analysis demonstrated that TRF2 is overexpressed in liver cancer and that high expression is associated with poor prognosis. Flavokavain B derivative FKB04 potently inhibited TRF2 expression in liver cancer cells while having limited effects on the other five shelterin subunits. Moreover, FKB04 treatment induced telomere shortening and increased the amounts of telomere-free ends, leading to the destruction of T-loop structure. Consequently, FKB04 promoted liver cancer cell senescence without modulating apoptosis levels. In corroboration with these findings, FKB04 inhibited tumor cell growth by promoting telomeric TRF2 deficiency-induced telomere shortening in a mouse xenograft tumor model, with no obvious side effects. These results demonstrate that TRF2 is a potential therapeutic target for liver cancer and suggest that FKB04 may be a selective small-molecule inhibitor of TRF2, showing promise in the treatment of liver cancer.